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01-11-2004 | Original Investigation

Thrombin induces Sp1-mediated antiviral effects in cytomegalovirus-infected human retinal pigment epithelial cells

Authors: Martin Scholz, Jens-Uwe Vogel, Gerold Höver, Susanna Prösch, Ruslan Kotchetkov, Jaroslav Cinatl, Frank Koch, Hans Wilhelm Doerr, Jindrich Cinatl Jr.

Published in: Medical Microbiology and Immunology | Issue 4/2004

Abstract

Human cytomegalovirus (HCMV) retinitis causing retinal detachment and destruction of the blood-retina barrier is closely related to retinal hemorrhage/coagulation. However, the effects of procoagulants on HCMV (re)activation in retinal cells have not been investigated yet. Therefore, we studied whether thrombin modulates the expression of HCMV immediate early (IE) and late (L) genes in cultured human retinal pigment epithelial cells (RPE). Thrombin specifically stimulated the protease-activated receptor-1 (PAR-1) on RPE and, surprisingly, inhibited basal and 12,0-tetradecanoylphorbol 13-acetate-stimulated HCMV IE gene expression in infected RPE. On the other hand, HCMV strongly induced Sp1 DNA binding activity, which was prevented by thrombin/PAR1-mediated Sp1 hyperphosphorylation. Our data suggest that thrombin/PAR-1 may inhibit Sp1-dependent HCMV replication, which might be an important regulatory mechanism for HCMV persistence and replication in RPE.

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Title: Thrombin induces Sp1-mediated antiviral effects in cytomegalovirus-infected human retinal pigment epithelial cells
Authors: Martin Scholz
Jens-Uwe Vogel
Gerold Höver
Susanna Prösch
Ruslan Kotchetkov
Jaroslav Cinatl
Frank Koch
Hans Wilhelm Doerr
Jindrich Cinatl Jr.
Publication date: 01-11-2004
Publisher: Springer-Verlag
Published in: Medical Microbiology and Immunology / Issue 4/2004
Print ISSN: 0300-8584
Electronic ISSN: 1432-1831
DOI: https://doi.org/10.1007/s00430-003-0194-x

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